AR101 Oral Immunotherapy for Peanut Allergy.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Oral food challenge failures among foods restricted because of atopic dermatitis.

BACKGROUND: Recent studies have suggested that removing foods from the diet to manage atopic dermatitis (AD), based on positive allergy test results, may lead to immediate allergic reactions on reintroduction of that food. OBJECTIVE: To examine the frequency of oral food challenge (OFC) failures among foods removed from the diet as suspected AD triggers, focusing on the 5 major food allergens in the United States. METHODS: OFCs to egg, milk, peanut, soy, and wheat, performed from 2008 to 2014, at a children's hospital's allergy clinics, were reviewed. OFCs were offered based on history and laboratory values. Reasons for food avoidance were classified as food allergy (IgE-mediated reaction occurring within 2 hours); sensitization only (lack of introduction because of positive test results); and removal because of test results during AD evaluation. RESULTS: There were 442 OFCs performed, with 89 failures (20.1%). Reasons for OFCs included a history of food allergy (320 of 442 [72.4%]), food sensitization without any introduction (77 of 442 [17.4%]), and AD (45 of 442 [10.2%]). OFC failures among those who had food allergy (70 of 320 [21.9%]), sensitization only (13 of 77 [16.9%]), and suspected AD trigger (6 of 45 [13.3%]) did not significantly differ (P = .63). Wheat was more likely to be avoided than the other 4 foods for AD concerns (P < .001). CONCLUSION: The frequency of OFC failure among those who removed foods suspected as AD triggers was 13.3%, indicating a loss of tolerance. Restriction of foods to manage AD must be done with caution and close monitoring.

Peanut Allergy: An Epidemiologic Analysis of a Large Database.

OBJECTIVE: To confirm new observations on peanut allergy and answer current concerns that families and healthcare providers have about peanut allergy. STUDY DESIGN: Children who presented with a story of peanut allergy or peanut sensitization were asked to participate in a registry, which allowed an analysis focused on questions that a food allergy support group had about children with peanut allergy or sensitization. RESULTS: A total of 1070 children were entered into the registry over 5 years. Two-thirds had a reaction to peanut. Children with peanut allergy were predominantly male (63%), white (78%), and with private health insurance (80%). Most reactions involved the skin (55%) and anaphylaxis occurred in 35%. The median age of a reaction was 1 year old. Atopic dermatitis was noted in 60% and asthma in 41%. Additional food allergy was noted in 58%. When second exposures occurred 28% had a more severe reaction. Skin test size did not differentiate the type of a reaction and children with anaphylaxis had slightly higher specific IgE levels. Severe reactions with inadvertent exposure in children who were peanut sensitized was rare (<1%). CONCLUSIONS: The strategies for peanut allergy prevention and treatment have evolved. The data obtained in this large registry can answer many questions that families and healthcare providers have during this transition.

Multisystem reactions during egg oral food challenges may be associated with less severe reactions on initial presentation.

In this study, we assessed whether multisystem reactions to egg and extensively-heated (EH) egg during OFCs were associated with a history of multisystem reactions. Records of children, who underwent OFC to egg or EH egg over a five-year period were reviewed. Of the 120 challenges, 26 (21.67 %) failed, with 38.4 % (10/26) having multisystem reactions. Of the 13 who had multisystem reactions on initial presentation, only two (15.4 %) had a similar OFC outcome. Eighty percent (8/10) of those who had a multisystem OFC reaction had a less severe initial presentation. Initial and OFC multisystem reactions were not associated with each other.

Relationship of adherence to pediatric asthma morbidity among inner-city children.

OBJECTIVES: Morbidity from asthma among children is one of the most important US health concerns. This study examines the relationship of baseline nonadherence to subsequent asthma morbidity among inner-city children. METHODS: A multisite, prospective, longitudinal panel study was conducted of 1199 children who were aged 4 to 9 years and had asthma and their caregivers, most of whom were parents, in emergency departments and clinics at 8 research centers in 7 US metropolitan inner-city areas. Nine morbidity indicators were collected at 3, 6, and 9 months after baseline, including hospitalizations, unscheduled visits, days of wheeze/cough, and days of reduced activities. RESULTS: Children whose caregivers scored high on a new measure, Admitted Nonadherence, experienced significantly worse morbidity on 8 of the 9 measures. Children who scored high on a new Risk for Nonadherence measure experienced significantly worse morbidity on all 9 morbidity measures. Multiple and logistic regressions found that the adherence measures had independent significant effects on morbidity. Combining the measures improved estimates of morbidity: children whose caregivers were poor on either adherence measure had worse morbidity than those with good adherence on both, eg, rate of hospitalization was twice as high, they missed more than twice as much school, had poorer overall functioning, and experienced more days of wheezing and more restricted days of activity. CONCLUSIONS: Risk for Nonadherence and Admitted Nonadherence independently and jointly predicted subsequent asthma morbidity. Targeting risks for nonadherence may be an effective intervention strategy. Most risks can be controlled by physicians through reducing the complexity of asthma regimens, communicating effectively with caregivers about medication use, and correcting family misconceptions about asthma medication side effects.